Usage
- Medical Conditions: Amodiaquine is prescribed for the treatment of uncomplicated Plasmodium falciparum malaria, particularly in regions where chloroquine resistance is prevalent. It can also be used for other Plasmodium species when chloroquine is ineffective. It’s typically administered in combination with artesunate. It is not recommended for malaria prophylaxis.
- Pharmacological Classification: Antimalarial, 4-aminoquinoline.
- Mechanism of Action: Amodiaquine inhibits heme polymerase, preventing the detoxification of heme into hemozoin within the malaria parasite. Accumulation of heme is toxic to the parasite, leading to its death.
Alternate Names
- International/Regional Variations: Amodiaquine hydrochloride.
- Brand Names: Camoquin, Flavoquine, Basoquin (in combination with artesunate as Artesunate Amodiaquine Winthrop, ASAQ, or AS/AQ).
How It Works
- Pharmacodynamics: Amodiaquine exerts its antimalarial effect by interfering with the parasite’s ability to detoxify heme. This leads to heme buildup, which is toxic to the parasite. The primary active metabolite, desethylamodiaquine (DEAQ), also contributes to the antimalarial activity. Amodiaquine is thought to be three times more potent than DEAQ.
- Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration.
- Metabolism: Extensively metabolized in the liver primarily by CYP2C8 to DEAQ.
- Elimination: Primarily through hepatic excretion; renal elimination plays a minor role.
Dosage
Standard Dosage
Adults: 10 mg/kg (amodiaquine base) daily for 3 days, usually administered in combination with artesunate (4mg/kg daily for 3 days).
Special Cases:
- Elderly Patients: Use with caution due to potential age-related decrease in hepatic function.
- Patients with Renal Impairment: Caution is advised; dosage adjustment may be required in severe impairment.
- Patients with Hepatic Dysfunction: Use with caution due to the risk of hepatotoxicity; dosage adjustment may be necessary.
- Patients with Comorbid Conditions: Exercise caution in patients with G6PD deficiency. Avoid in those with a history of agranulocytosis.
Clinical Use Cases
Amodiaquine, in combination with artesunate, is primarily used for the oral treatment of uncomplicated malaria. It is not typically indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations involving malaria. Parenteral artesunate is generally preferred for severe malaria.
Dosage Adjustments
Dose adjustments are necessary for patients with hepatic or renal impairment. Consider drug interactions (e.g., with efavirenz, nevirapine, and drugs that prolong the QT interval) when determining the appropriate dosage.
Side Effects
Common Side Effects: Nausea, vomiting, abdominal discomfort, headache, dizziness, fatigue, pruritus, cough, and insomnia.
Rare but Serious Side Effects:
Hepatotoxicity (including hepatitis and liver failure), agranulocytosis, neutropenia, hypersensitivity reactions (including rash, itching, and anaphylaxis), QTc prolongation, neurologic effects (blurred vision, blindness), and cardiovascular abnormalities.
Long-Term Effects: Ocular toxicity (including retinopathy) with prolonged use.
Adverse Drug Reactions (ADR): Agranulocytosis, hepatotoxicity, and severe hypersensitivity reactions.
Contraindications
- Known hypersensitivity to amodiaquine or related compounds.
- Severe liver impairment.
- History of agranulocytosis or other severe hematological disorders.
- Concomitant use with efavirenz.
Drug Interactions
- CYP450 Interactions: Metabolized by CYP2C8; inhibitors (e.g., gemfibrozil) may increase amodiaquine levels, while inducers (e.g., rifampin) may decrease levels.
- Other Interactions:
- Antimalarials (e.g., mefloquine): Increased risk of QTc prolongation.
- Antiretrovirals (e.g., efavirenz, nevirapine): Reduced efficacy of amodiaquine.
- Drugs that prolong the QT interval (e.g., amiodarone, macrolides, fluoroquinolones): Increased risk of QTc prolongation.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Limited safety data in the first trimester; use with caution. Generally considered safe during the second and third trimesters if benefits outweigh risks.
- Breastfeeding: Small amounts are excreted in breast milk. Acceptable to use in breastfeeding women with older infants if necessary.
Drug Profile Summary
- Mechanism of Action: Inhibits heme polymerase in malaria parasites.
- Side Effects: Nausea, vomiting, abdominal pain, headache, dizziness, pruritus, hepatotoxicity, agranulocytosis, hypersensitivity reactions.
- Contraindications: Hypersensitivity, severe liver disease, history of agranulocytosis, concomitant efavirenz.
- Drug Interactions: CYP2C8 inhibitors/inducers, other antimalarials, antiretrovirals (efavirenz, nevirapine), drugs prolonging QT interval.
- Pregnancy & Breastfeeding: Use with caution in the first trimester and during breastfeeding.
- Dosage: 10mg/kg (base) daily for 3 days in combination with artesunate.
- Monitoring Parameters: Liver function tests, complete blood count.
Popular Combinations
- Artesunate + Amodiaquine (ASAQ): The most common combination, offering synergistic antimalarial activity.
Precautions
- General Precautions: Assess liver and kidney function before starting treatment. Monitor for hematological abnormalities and hypersensitivity reactions.
- Specific Populations: Caution in pregnant women (especially first trimester), breastfeeding mothers, children (ensure accurate dosing), and the elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amodiaquine?
A: The recommended dosage is 10 mg/kg (amodiaquine base) daily for 3 days, given in combination with artesunate (4mg/kg/day for 3 days).
Q2: What are the most common side effects of Amodiaquine?
A: Common side effects include nausea, vomiting, abdominal discomfort, headache, dizziness, fatigue, itching, cough, and insomnia.
Q3: What are the serious side effects of Amodiaquine?
A: Serious side effects include hepatotoxicity, agranulocytosis, neurologic symptoms (blurred vision, blindness), and hypersensitivity reactions.
Q4: Can Amodiaquine be used in pregnancy?
A: Limited safety data are available for the first trimester. Amodiaquine may be used during the second and third trimesters if benefits outweigh the risks.
Q5: Can Amodiaquine be used during breastfeeding?
A: Small amounts are excreted in breast milk. Generally, acceptable for use in mothers breastfeeding older infants if alternative treatments are unavailable.
Q6: What drug interactions should I be aware of with Amodiaquine?
A: Significant interactions exist with efavirenz, nevirapine, and drugs that prolong the QT interval (e.g., macrolides, fluoroquinolones). Amodiaquine is metabolized by CYP2C8, so inhibitors and inducers of this enzyme can alter its levels.
Q7: What is the mechanism of action of Amodiaquine?
A: Amodiaquine inhibits heme polymerase, preventing heme detoxification within the malaria parasite, leading to its death.
Q8: Is Amodiaquine effective against all types of malaria?
A: It is primarily used for P. falciparum malaria, particularly where chloroquine resistance exists. It can be used for other Plasmodium species when chloroquine is ineffective.
Q9: Can Amodiaquine be used for malaria prevention?
A: No, it is not recommended for malaria prophylaxis due to the risk of long-term side effects.
Q10: What monitoring parameters are important during Amodiaquine treatment?
A: Liver function tests and complete blood count should be monitored, particularly during prolonged therapy.
